Summary of Work: A series of projects to elucidate the physiological functions of the individual cyclooxygenase (COX) isoforms are ongoing with the COX knockout mice. Mice deficient in both COX-1 and COX-2 have been produced. These mice, and mice carrying only a single copy of one of the COX genes, are being used to determine the physiological roles of the individual COX isoforms and to elucidate the ways in which the two isoforms act individually or in conjunction. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus, but otherwise appear developmentally normal. We have found that COX-2 is the isoform primarily responsible for the closure of the ductus and that COX-2, but not COX-1, is induced in the contracting smooth mucles of the ductus